Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMIOGBU)

Drug Name

Bosentan Drug Info

Synonyms

Actelion; Bosentanum; Tracleer; Bosentan (INN); KS-5062; Ro 47-0203; Tracleer (TN); Bosentan [USAN:INN:BAN]; Ro 47-0203/039; Ro-47-0203; Ro-47-0203/029; Ro-47-0203/039; P-tert-Butyl-N-[6-(2-hydroxyethoxy); P-tert-Butyl-N-(6-(2-hydroxyethoxy)-5-(o-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl)benzenesulfonamide; 4-(1,1-Dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-(2,2'-bipyrimidin)-4-yl) benzenesulfornamide; 4-(1,1-Dimethylethyl)-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-(2,2'-bipyrimidin)-4-yl)benzenesulfornamide; 4-t-butyl-N-(6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl)benzenesulfonamide; 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2,2'-bipyrimidin-4-yl]benzenesulfonamide; 4-tert-butyl-N-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide

Indication

Disease Entry	ICD 11	Status	REF
Pulmonary arterial hypertension	BB01.0	Approved	[1]
Pulmonary hypertension	BB01	Approved	[2]
Scleroderma	4A42	Investigative	[2]

Therapeutic Class

Antihypertensive Agents

Cross-matching ID

PubChem CID: 104865
ChEBI ID: CHEBI:51450
CAS Number: CAS 147536-97-8
TTD Drug ID: DMIOGBU
VARIDT Drug ID: DR00288
INTEDE Drug ID: DR0222
ACDINA Drug ID: D00074

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Endothelin A receptor (EDNRA)	TTKRD0G	EDNRA_HUMAN	Modulator	[3]
Endothelin B receptor (EDNRB)	TT3ZTGU	EDNRB_HUMAN	Modulator	[3]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	Highest Status	REF
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Approved	[4]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Approved	[4]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Approved	[4]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Approved	[5]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Approved	[6]

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The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Endothelin A receptor (EDNRA)	DTT	EDNRA	3.776	4.505	5.121	3.536
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTP	OATP2B1	8.165	6.597	6.591	6.397
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DTP	OATP1B3	8.873	2.17	2.485	3.322
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DTP	OATP1B1	9.79	0.485	3.511	2.07
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	11.76	5.931	6.164	9.423
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	11.692	6.58	4.984	9.089

Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease

Pulmonary arterial hypertension

ICD Disease Classification

BB01.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Endothelin A receptor (EDNRA)	DTT	EDNRA	3.19E-05	-2.69	-1.71
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTP	OATP2B1	2.89E-11	-1.11E+00	-2.81E+00
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DTP	OATP1B3	2.08E-04	3.94E-02	1.17E-01
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DTP	OATP1B1	7.59E-01	-3.08E-02	-1.64E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	4.97E-04	-1.04E+00	-1.67E+00
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.10E-01	-1.23E-01	-2.88E-01

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 3494).
2	Bosentan FDA Label
3	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
4	Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007 Aug;35(8):1400-7.
5	Bosentan is a substrate of human OATP1B1 and OATP1B3: inhibition of hepatic uptake as the common mechanism of its interactions with cyclosporin A, rifampicin, and sildenafil. Drug Metab Dispos. 2007 Aug;35(8):1400-7.
6	Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Clin Pharmacokinet. 2003;42(3):293-301.